Abstract
Chikungunya virus (CHIKV) is a positive-sense RNA virus transmitted by Aedes mosquitoes. CHIKV is a reemerging Alphavirus that causes acute febrile illness and severe and debilitating polyarthralgia of the peripheral joints. Huge epidemics and the rapid spread of CHIKV seen in India and the Indian Ocean region established CHIKV as a global health concern. This concern was further solidified by the recent incursion of the virus into the Western hemisphere, a region without pre-existing immunity. Nonhuman primates (NHPs) serve as excellent animal models for understanding CHIKV pathogenesis and pre-clinical assessment of vaccines and therapeutics. NHPs present advantages over rodent models because they are a natural amplification host for CHIKV and they share significant genetic and physiological homology with humans. CHIKV infection in NHPs results in acute fever, rash, viremia and production of type I interferon. NHPs develop CHIKV-specific B and T-cells, generating neutralizing antibodies and CHIKV-specific CD4+ and CD8+ T-cells. CHIKV establishes a persistent infection in NHPs, particularly in cynomolgus macaques, because infectious virus could be recovered from spleen, liver, and muscle as late as 44 days post infection. NHPs are valuable models that are useful in preclinical testing of vaccines and therapeutics and uncovering the details of CHIKV pathogenesis.
Highlights
Chikungunya virus (CHIKV) is a mosquito-transmitted RNA virus that causes acute febrile illness and severe debilitating joint pain
Results from these Nonhuman primates (NHPs) studies, along with what has been reported during human infection, support the idea that during CHIKV infection at peak viremia, immune cells are recruited from the blood into the surrounding tissues to control viral loads and reduce dissemination
In rhesus macaques at 7 dpi, CHIKV was detected in joints, musculoskeletal tissues, heart, lung, liver, kidney, and lymphoid tissues, demonstrating the ability of CHIKV to disseminate to various tissues in this macaque model [63]
Summary
Chikungunya virus (CHIKV) is a mosquito-transmitted RNA virus that causes acute febrile illness and severe debilitating joint pain. Asia because of isolation of infectious virus from NHPs in Malaysia [35] and CHIKV-specific antibodies present in Asian NHPs [36,37]; the nature of the transmission cycle in Asia needs to be more thoroughly studied Both humans and NHPs serve as amplification hosts for CHIKV, highlighting the importance of studying CHIKV in NHPs. Genetic analysis of several CHIKV isolates revealed that there are three distinct CHIKV lineages: the Asian clade, West African clade, and East/Central/South. Other CHIKV isolates commonly used in NHP studies include the Senegal isolate CHIKV-37997 from the West African clade and the ECSA isolate CHIKV-DHS-4263 obtained from a traveler in India during the Indian Ocean Island outbreak [42]. The circulating strain in the Caribbean stems from the Asian lineage, but the Caribbean isolates have not been used in any reported NHP studies [43]
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